Lithium Chloride Slows Cartilage Degradation

It turns out that a drug used to stabilize moods—lithium chloride—may be helpful in treating osteoarthritis (OA). New research from Queen Mary University of London (QMUL) and the University of Otago in New Zealand has found that this drug slowed the degradation associated with OA.

According to the July 16, 2015 news release, “The study used bovine cartilage samples exposed to inflammatory molecules to mimic the effects of arthritis and then treated the tissue with lithium chloride. The researchers demonstrated that this already commonly used drug could be used to prevent the degradation and loss of mechanical integrity of cartilage in patients with arthritis. The researchers also found that, contrary to some reports, long-term dietary use of lithium did not cause arthritis.”

Professor Martin Knight, co-author of the research, said, “While we’re still at an early stage in researching lithium’s effects on cartilage and its suitability as a treatment, the possibility that an already widely available pharmaceutical could slow its progress is a significant step forward.”

Professor Knight told OTW, “The most surprising thing was the strength of this effect and the response to long term dietary intake. Others have suggested that lithium may prevent cartilage catabolic signalling in vitro and degradation when injected into a joint. However separate studies indicate that long term dietary lithium may be damaging to cartilage by disrupting the synthesis of proteoglycan which forms the tissue extracellular matrix and contributes to cartilage mechanical functionality. We show for the first time that long term dietary lithium does not lead directly to cartilage damage. Furthermore, we show that in response to inflammatory cytokine, IL1B, lithium prevents the associated catabolic signalling and the resulting cartilage degradation and most importantly the loss of biomechanical properties which are so essential for cartilage function.”

“For my group, the next steps are to explore how lithium is having this effect and the specific involvement of a fascinating but poorly understood hair-like cellular structure called the primary cilium (cilia in plural from the Latin for eye lashes). We are interested in whether lithium is regulating the structure of the primary cilium on each cartilage cell and that is then changing some of the cellular signalling events that lead to cartilage degradation and arthritis. Arthritis is associated with a reduction in the length of primary cilia in cartilage cells whereas lithium causes an elongation of the cilia. We currently have a major Medical Research Council (MRC) grant which is investigating the role of primary cilia in osteoarthritis. What would be really exciting is if we could find other compounds like lithium (but without some of the associated effects) which would change primary cilia structure and thereby provide a novel treatment for arthritis. To do this we are looking to collaborate with pharmaceutical companies to screen possible novel compounds for their effect on primary cilia.”

“Collaboration with orthopaedic surgeons is very important for this research. We are working with Mr. Ramachandren and his team at Barts and the London NHS trust. My group would welcome any clinicians interested in doing a research fellowship in this exciting and rapidly expanding area looking at the role of primary cilia in cartilage health and disease and the potential of novel ciliotherapy treatments for OA.”